Shexiang Baoxin pill attenuates valvular dysfunction in rats via the regulation of ferroptosis
10.3969/j.issn.1671-7856.2025.09.003
- VernacularTitle:麝香保心丸通过调控铁死亡减轻大鼠瓣膜功能障碍的作用机制研究
- Author:
Zhihao CHEN
1
;
Zhenzhen LAN
;
Xincan LIU
;
Luyao LIU
;
Xueyan JIAO
;
Yifan ZHANG
;
Yun CHEN
Author Information
1. 河南中医药大学第一附属医院心脏中心,郑州 450000;河南中医药大学第一临床医学院,郑州 450046
- Publication Type:Journal Article
- Keywords:
aortic valve injury;
Shexiang Baoxin pill;
oxidative stress;
iron homeostasis;
ferroptosis;
osteogenic differentiation
- From:
Chinese Journal of Comparative Medicine
2025;35(9):25-36
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and underlying mechanisms of Shexiang Baoxin pill(SBP)on wire injury-induced valvular dysfunction in rats.Methods A rat model of aortic valve injury was established using a standardized wire injury method.Animals were randomly divided into control,sham,model,and SBP low-,medium-,and high-dose(SBP-L,SBP-M,SBP-H)intervention groups.Aortic valve function was evaluated using echocardiography.Histopathological changes were assessed using hematoxylin-eosin(HE)and Masson's staining.Serum levels of lipid peroxides(LPO),malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),and total iron were measured using biochemical assays.Expression levels of ferroptosis-related proteins(ACSL4,SLC7A11,and GPX4)and osteogenic markers(RUNX2 and BMP2)in valve tissues were detected through Western blot and RT-qPCR.Results The SBP-M and SBP-H groups showed significantly higher aortic valve orifice areas((3.70±0.04)mm2 and(3.90±0.11)mm2 vs(2.25±0.37)mm2,P＜0.0001),lower transvalvular pressure gradients((0.52±0.09)mmHg and(0.49±0.13)mmHg vs(0.90±0.17)mmHg,P＜0.01),and lower aortic valve peak flow velocities((68.83±4.98)cm/s and(63.61±11.43)cm/s vs(87.14±11.22)cm/s,P＜0.05,P＜0.01)than those in the model group.HE and Masson's staining result demonstrated that SBP alleviates valve thickening and fibrosis(fibrotic area:(35.98±5.2)5％vs(53.01±2.44)％,P＜0.01).Biochemical tests showed that SBP reduces serum levels of lipid peroxidation products(LPO and MDA)and total iron ions while increasing SOD and GSH levels(P＜0.001,P＜0.0001).SBP downregulated the ferroptosis-related protein ACSL4(P＜0.01),upregulated the anti-ferroptosis proteins SLC7A11 and GPX4(P＜0.05,P＜0.01),and inhibited the expression of the osteogenic molecules RUNX2 and BMP2(P＜0.05,P＜0.01,P＜0.0001).Conclusions SBP may alleviate mechanical injury-induced valve dysfunction in rats through the modulation of oxidative stress and restoration of iron homeostasis.These findings provide experimental evidence for the role of SBP in the early intervention of valvular disease.The precise active components,molecular targets,and clinical translation of SBP require further investigation.
